Project summary Dr Michelle Groome is a senior research officer at the Respiratory and Meningeal Pathogens Research Unit based at the Chris Hani Baragwanath Academic Hospital, South Africa. She has an undergraduate medical degree and a Masters in Science degree in Epidemiology and Biostatistics from the University of the Witwatersrand. She has recently submitted her PhD thesis, assessing the impact and effectiveness of the oral rotavirus vaccine among children in an African setting. She has published in several peer- reviewed international journals and presented at local and international conferences. Her continued growth and productivity is evidence of her commitment to a career in diarrhoeal diseases and vaccine research in South Africa. She would like to build on her existing rotavirus vaccine portfolio in children as well as expand her research to include other important enteric pathogens and groups at risk for diarrhoea, for example the elderly and HIV-infected adults. Research is needed to describe the epidemiology and aetiology of diarrhoea in different age groups and to assess interventions, especially vaccines, to prevent diarrhoeal disease in South Africa. With dedicated research time she can expand her knowledge in key areas such as vaccine immunology, laboratory testing methods, statistical analysis, grant writing and presentation skills. Scientific interactions with fellow researchers in the enteric vaccine field will identify potential collaborators in Africa and further afield. Together with an experienced team of mentors and collaborators both in South Africa and the Unites States, she will acquire the skills necessary to establish herself as an independent researcher with the overall long-term goal of establishing a dedicated enteric vaccines unit in Johannesburg, South Africa. Diarrhoeal disease remains a leading cause of morbidity and mortality in children <5 years of age, especially in low- and middle-income countries. Vaccination against rotavirus has the potential to provide a cost- effective public health impact and substantially reduce the burden of diarrhoeal disease, but the vaccine does not perform as well in developing countries as in high-income countries. Understanding the reasons behind the lower vaccine efficacy is critical as even small improvements in efficacy could lead to substantial decreases in the number of deaths and hospitalisations caused by rotavirus. The goals of the proposed research are to describe the aetiology of diarrhoeal hospitalisations in children <5 years of age, especially infections with more than one diarrhoeal pathogen detected, and to understand safety and factors influencing the immune response to an oral enteric vaccine in an African setting. Although these data will only be generated in South Africa, the findings could be applicable to children across Africa. The proposed research plan will build on previous work, and aims to assess the effect of seasonality, maternal rotavirus-specific antibodies, enteric co-infections and genetic polymorphisms on the immune response to the rotavirus vaccine and/or risk of hospitalisation for rotavirus gastroenteritis. Results could inform policy decisions as well as guide the future research agenda pertaining to use and development of rotavirus vaccines as well as other enteric vaccines currently under development. Global data currently suggests that rotavirus vaccines may be associated with a small risk of intussusception, a cause of intestinal obstruction in young children. Identification of infectious pathogens and inflammatory markers associated with intussusception will provide insight into the underlying aetiology of this condition, which has important implications not just for rotavirus vaccines but also possibly for other live-attenuated enteric vaccine candidates.